Gap junction blockers attenuate beta oscillations and improve forelimb function in hemiparkinsonian rats
Sujoy Phookan1, Alexander C Sutton1, Ian Walling1
1Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY USA.
Experimental Neurology
|January 28, 2015
Summary
Gap junctions contribute to beta oscillations in the basal ganglia of Parkinson's disease models. Inhibiting these junctions reduced oscillations and improved motor function in rats, suggesting a therapeutic target.
Area of Science:
- Neuroscience
- Neurodegenerative Diseases
- Cellular Electrophysiology
Background:
- Parkinson's disease (PD) is characterized by motor deficits, with dominant beta (β) oscillations (12-30Hz) in basal ganglia (BG) linked to dysfunction.
- The precise cellular and network mechanisms underlying these β oscillations in PD remain unclear.
- Gap junctions (GJs) are hypothesized to play a role in generating these pathological oscillations.
Purpose of the Study:
- To investigate the role of gap junctions (GJs) in mediating β oscillations within the basal ganglia (BG) of hemiparkinsonian rats.
- To determine if inhibiting GJ activity can disrupt neuronal synchrony, reduce β oscillations, and improve motor function.
- To explore the potential of GJ modulation as a therapeutic strategy for Parkinson's disease.
Main Methods:
- Administered GJ blockers (carbenoxolone [CBX] or octanol) systemically and directly into the globus pallidus externa (GPe) of anesthetized hemiparkinsonian rats.
- Utilized in vivo electrophysiology to measure changes in β oscillatory activity in the GPe.
- Assessed motor function using the step test and induced oscillations/akinesia in naive rats using trimethylamine (TMA).
Main Results:
- Systemic CBX and octanol treatments significantly attenuated normalized GPe β oscillatory activity in hemiparkinsonian rats.
- Direct GPe injection of CBX reduced β oscillations, while TMA injection in naive rats induced β oscillations and contralateral akinesia.
- Systemic CBX administration improved left forepaw akinesia in hemiparkinsonian rats.
Conclusions:
- Gap junctions (GJs) significantly contribute to the generation of β oscillations in the globus pallidus externa (GPe) of hemiparkinsonian rats.
- Inhibiting GJ activity effectively reduces pathological β oscillations and ameliorates motor deficits associated with Parkinson's disease models.
- Targeting GJ function presents a promising avenue for developing novel therapeutic interventions for Parkinson's disease.
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